RNA silencing is a defense mechanism of eukaryotic cells that recognizes and destroys invasive nucleic acids such as viruses, transposons, and transgenes. (Ding, 2010; Ding and Voinnet, 2007; Ruiz-Ferrer and Voinnet, 2009.) Intracellular initiation of RNA silencing can be triggered by double-stranded RNA (dsRNA), which is processed by Dicer RNase into small interfering RNAs (siRNAs) of ˜21 nucleotides (nt). siRNAs are then incorporated into RNA-induced silencing complexes (RISC) capable of guiding cycles of sequence-specific RNA degradation. Replication of RNA viral genomes often involves dsRNA intermediates that are susceptible degradation by the RNA silencing mechanism. Some RNA viral genomes encode protein suppressors of RNA silencing. (Ding, 2010; Ruiz-Ferrer and Voinnet, 2009.)
More than forty suppressor of RNA silencing proteins have been identified from plant and animal viruses. (Ding, 2010; Li and Ding, 2006; Ruiz-Ferrer and Voinnet, 2009.) These suppressor proteins can be categorized according to three, currently-identified mechanisms as follows: (i) suppression of siRNA production (e.g. HC-Pro of Potyviruses) (Llave et al., 2000); (ii) sequestration of siRNAs (e.g. p19 of Tombusviruses) (Lakatos et al., 2004; Vargason et al., 2003); and (iii) Inhibition of systemic silencing (e.g. p25 of Potato virus X) (Voinnet et al., 2000). A major function of the viral RNA silencing suppressors is to act as dsRNA-binding proteins (Li and Ding, 2006; Ruiz-Ferrer and Voinnet, 2009).
Tombusvirus p19 is a suppressor of RNA silencing that binds to 21 nt duplex siRNAs with high affinity and also binds 22 nt dsRNAs, but with lower affinity. p19 has been categorized as suppressing RNA silencing by sequestering 21 nt duplex siRNAs and prevent their incorporation into the RISC. (Lakatos et al., 2004; Vargason et al., 2003.)